Affinage

CCT3

T-complex protein 1 subunit gamma · UniProt P49368

Round 2 corrected
Length
545 aa
Mass
60.5 kDa
Annotated
2026-04-28
129 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCT3 is the gamma subunit of the eukaryotic cytosolic chaperonin TRiC/CCT, an ATP-dependent protein-folding machine that is essential for proteostasis, cytoskeletal integrity, and cell division. Within the hetero-octameric ring, CCT3's apical domain faces outward and confers unique substrate specificity for Gln/Asn-rich proteins; the intact complex catalyzes ATP-driven folding of actin with first-order kinetics, and CCT3 loss disrupts tubulin/microtubule organization, myelination, and neuromuscular junction refinement in vertebrate models (PMID:16762366, PMID:23112166, PMID:41680121). Beyond canonical chaperonin substrates, CCT3 stabilizes YAP and TFCP2 by blocking PCBP2-mediated ubiquitination, facilitates XPO1-dependent nuclear export of tumor suppressors, interacts with ACTN4 to impede transferrin receptor recycling and thereby suppress ferroptosis, and functions as a non-canonical RNA-binding protein regulating the lncRNA LINC00326 to control lipid metabolism (PMID:31501420, PMID:41732260, PMID:39210442, PMID:35022268). The isolated CCT3 apical domain inhibits tau aggregation through a saturating elongation–fragmentation mechanism distinct from that of other CCT subunits (PMID:40400346).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Chromosomal mapping of CCT3 to 1q23 established that TRiC subunits are encoded at dispersed loci, raising the question of how subunit-specific functions are regulated.

    Evidence FISH mapping of the human CCT3/TRIC5 cDNA

    PMID:8001976

    Open questions at the time
    • No functional data at this stage
    • Regulatory elements of the locus uncharacterized
  2. 1996 High

    Cloning of human, Drosophila, and Xenopus CCT3 orthologs revealed a highly conserved ~60 kDa chaperonin subunit with broad tissue expression and elevated levels in germline-rich tissues, establishing CCT3 as a core TRiC component.

    Evidence cDNA cloning, sequence alignment, Northern blots across species

    PMID:8573069 PMID:8666276 PMID:8950171

    Open questions at the time
    • No biochemical activity demonstrated
    • Subunit-specific substrate preferences unknown
  3. 2006 High

    Reconstitution of actin folding with purified CCT complex (tagged at the CCT3 apical domain) demonstrated ATP-driven first-order folding kinetics and sequence-specific substrate recognition, providing the first quantitative enzymology for TRiC-mediated folding.

    Evidence Affinity-purified yeast CCT, quantitative in vitro actin folding assay with beta-actin mutants

    PMID:16762366

    Open questions at the time
    • Contribution of individual subunits to the folding cycle not dissected
    • Tubulin folding kinetics by CCT not similarly quantified
  4. 2012 High

    An ATP-binding-site mutation in CCT3 (but not CCT6) specifically impaired binding of Gln/Asn-rich substrates and induced P-body formation, revealing that CCT3 uniquely handles Q/N-rich proteome segments among the eight CCT subunits.

    Evidence Yeast mutagenesis, high-throughput microscopy, in vitro gel-shift assay

    PMID:23112166

    Open questions at the time
    • Structural basis for Q/N-rich selectivity unresolved at atomic level
    • Whether CCT3 directly contacts substrate Q/N segments vs. allosterically enabling folding not distinguished
  5. 2015 Medium

    CCT3 depletion in hepatocellular carcinoma cells revealed a direct role in mitotic spindle integrity and kinetochore–microtubule attachment, connecting the chaperonin to cell division beyond its general proteostasis function.

    Evidence siRNA knockdown, immunofluorescence of spindle/kinetochore, drug sensitization with vincristine

    PMID:26739059

    Open questions at the time
    • Whether the mitotic defect reflects loss of tubulin/actin folding or a distinct CCT3 client remains unclear
    • No identification of specific mitotic substrates of CCT3
  6. 2016 Medium

    Proteomic analysis of stress granule cores showed that the intact CCT complex inhibits stress granule assembly, extending TRiC function to RNA granule homeostasis.

    Evidence Super-resolution microscopy, quantitative proteomics of purified stress granule cores in human cells

    PMID:26777405

    Open questions at the time
    • CCT3-specific contribution vs. holo-complex activity not separated
    • Mechanism of stress granule inhibition (client folding vs. direct sequestration) not determined
  7. 2018 Medium

    Genetic and physical interaction between Drosophila CCT3 and FNDC3-ortholog MTGO demonstrated a chaperonin–client relationship required for neuromuscular junction development, providing the first in vivo neurodevelopmental phenotype for CCT3.

    Evidence Genetic epistasis, co-immunoprecipitation, confocal NMJ analysis in Drosophila

    PMID:30539716

    Open questions at the time
    • Whether CCT3 folds MTGO or acts in a non-canonical manner not resolved
    • Mammalian relevance not tested at that time
  8. 2019 Medium

    CCT3 was shown to stabilize oncoproteins YAP and TFCP2 by competitively blocking PCBP2-mediated ubiquitination, revealing a non-canonical chaperonin role in regulating Hippo-pathway effector turnover.

    Evidence Co-IP/mass spectrometry, ubiquitination assays, protein half-life measurements in liver cancer cells

    PMID:31501420

    Open questions at the time
    • Whether CCT3 acts as part of the holo-complex or as a free subunit in this context is unknown
    • E3 ligase responsible for PCBP2-directed ubiquitination not identified
  9. 2021 Medium

    Multiple cancer-cell studies converged on CCT3 as a proliferation-essential gene whose depletion arrests the cell cycle and induces apoptosis, acting upstream of CDK1 in melanoma and NFκB-p65 in breast cancer, while also perturbing mitochondrial membrane potential and amino acid homeostasis.

    Evidence shRNA/siRNA knockdown with rescue experiments (CDK1, NFκB-p65), flow cytometry, ROS/MMP assays, amino acid profiling across breast, prostate, melanoma, and cervical cancer lines

    PMID:32518527 PMID:33508424 PMID:34651664 PMID:35399722

    Open questions at the time
    • Direct folding clients mediating these diverse phenotypes remain unidentified
    • Whether proliferative effects are CCT3-specific or reflect loss of holo-CCT is not distinguished in most studies
  10. 2022 Medium

    CCT3 was identified as a non-canonical RNA-binding protein that regulates lncRNA LINC00326 independently of the chaperonin complex, controlling lipid accumulation and tumor growth in hepatocellular carcinoma.

    Evidence RBP-lncRNA interaction mapping, transcriptome sequencing, CRISPRa, in vivo tumor models

    PMID:35022268

    Open questions at the time
    • RNA-binding domain within CCT3 not mapped
    • Extent of the CCT3-regulated lncRNA repertoire unknown
  11. 2022 Medium

    CCT3 interaction with EIF3G in lung adenocarcinoma cells linked the chaperonin to translational control: CCT3 depletion destabilized EIF3G, reduced protein synthesis, and impaired glycolysis.

    Evidence Co-immunoprecipitation, glycolysis/ATP assays, EIF3G protein level analysis, xenograft

    PMID:35409343

    Open questions at the time
    • Whether CCT3 folds EIF3G as a classical client or stabilizes it post-folding not distinguished
    • Glycolytic impairment may be secondary to general translational deficit
  12. 2024 Medium

    CCT3 interaction with ACTN4 was shown to hinder TFRC recycling and iron endocytosis, establishing a ferroptosis-suppressive mechanism; this function is regulated by K6-linked deubiquitination at CCT3-K21.

    Evidence CRISPR screen, PTM omics, Co-IP, ferroptosis assays, in vivo xenograft in HCC

    PMID:39210442

    Open questions at the time
    • Identity of the deubiquitinase removing K6-linked ubiquitin from CCT3-K21 not determined
    • Whether ACTN4 is a direct folding substrate or a non-client partner is unclear
  13. 2024 Medium

    CCT3 was found to fold and stabilize XPO1, promoting nuclear export of tumor suppressors RB1 and p21 and thereby suppressing cellular senescence in renal carcinoma.

    Evidence Co-IP, GST pull-down, senescence assays, combined CCT3 knockdown with selinexor in xenograft

    PMID:41732260

    Open questions at the time
    • Whether XPO1 stabilization requires holo-CCT or CCT3 alone not tested
    • How CCT3 loss affects the broader nuclear export proteome is unexplored
  14. 2025 Medium

    The isolated CCT3 apical domain was shown to inhibit tau aggregation via a saturating elongation–fragmentation mechanism distinct from CCT7, providing subunit-resolution insight into TRiC's anti-amyloid activity.

    Evidence In vitro tau aggregation kinetics, negative-stain EM, coarse-grained MD simulation

    PMID:40400346

    Open questions at the time
    • Efficacy of the CCT3 apical domain against tau in cellular or animal models not tested
    • Binding site on tau not mapped at residue resolution
  15. 2026 High

    Zebrafish cct3 loss-of-function mutants established that CCT3 is essential for Schwann cell survival, myelination, NMJ refinement, and axonal organelle transport, with pathological features conserved in human TRiCopathy patient tissue.

    Evidence CRISPR/Cas9 knockout in zebrafish, confocal and electron microscopy, comparison with human patient tissue

    PMID:41680121

    Open questions at the time
    • Specific folding substrates whose misfolding drives Schwann cell death not identified
    • Whether CCT3 haploinsufficiency is sufficient for human neuropathy not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A systematic catalog of CCT3-specific folding clients versus holo-CCT clients remains absent, leaving uncertain which proliferative, metabolic, and neurodevelopmental phenotypes reflect loss of CCT3's unique substrate specificity versus general chaperonin dysfunction.
  • No proteome-wide identification of CCT3-specific vs. holo-CCT substrates
  • Structural basis of CCT3 apical domain selectivity for Q/N-rich and tau substrates not resolved at atomic level
  • Relative contributions of CCT3 as free subunit vs. within the complex in non-canonical functions (RNA binding, YAP stabilization) are unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 2 GO:0140657 ATP-dependent activity 2 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 3
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1430728 Metabolism 2 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2
Partners
ACTBACTN4EIF3GPCBP2TFCP2XPO1YAP1
Complex memberships
TRiC/CCT

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Human CCT3 (Cctg) gene was cloned and characterized, encoding a 544 amino acid ~60 kDa gamma subunit of the cytosolic chaperonin CCT complex. The predicted protein shares conserved domains with other TF55/TCP-1 family chaperonins including GroEL and Hsp60, and is highly conserved across mouse (98%), yeast (75%), and protozoa (76%). mRNA is expressed in numerous human and mouse tissues with higher levels in testis. cDNA library screening, PCR cloning, sequence analysis, Southern blot, Northern blot The Biochemical journal High 8573069
1994 The human homologue of mTRiC-P5 (CCT3/TRIC5) was mapped to chromosome 1q23 by fluorescence in situ hybridization, establishing its chromosomal location as distinct from TCP1 on chromosome 6. Fluorescence in situ hybridization (FISH), cDNA cloning Genomics High 8001976
1996 The Drosophila melanogaster Cctg gene (encoding CCT gamma, ortholog of human CCT3) was identified and characterized within P1 genomic clone DS05563, comprising four exons interrupted by three introns. The predicted 545 aa peptide shares 70% identity with human CCT3 and contains conserved chaperonin domains found in GroEL, mitochondrial Hsp60, and plant Rubisco binding protein. Genomic clone sequencing and structural analysis Gene Medium 8666276
1996 The Xenopus laevis CCT3 ortholog (XlCctg) encodes a 547 amino acid 60 kDa protein with high sequence identity to other CCT gamma homologues. XlCctg mRNA (2.1 kb) is expressed ubiquitously across X. laevis tissues but at significantly higher levels in the ovary compared with other tissues. cDNA cloning, Northern blot, library screening, PCR Biochimica et biophysica acta Medium 8950171
2006 A purification protocol for yeast CCT using the calmodulin binding peptide as an affinity tag inserted into an internal loop in the apical domain of the CCT3 subunit was developed. This CCT3 apical domain location is predicted to be on the outside of the double-ring assembly. Using purified yeast CCT, quantitative actin-folding assays showed that CCT catalyzes folding of both yeast ACT1p and human beta-actin with nearly identical rate constants (~0.03 min⁻¹). The folding reaction follows approximately first-order kinetics consistent with a binding pre-equilibrium followed by ATP-driven processing to native actin. Human beta-actin mutants D244S and G150P showed impaired folding, validating sequence-specific recognition by CCT. Affinity purification, quantitative in vitro actin folding assay, mutagenesis Journal of molecular biology High 16762366
2012 A Glu-to-Asp mutation in the ATP binding site of yeast CCT3 (but not CCT6) causes cytoplasmic foci (P-bodies) to form, where untranslated mRNAs accumulate. Structural modeling and analysis of protein level changes indicate that CCT3's ATP-binding site mutation specifically impairs its interaction with Gln/Asn-rich segments enriched in P-body proteins. An in vitro gel-shift assay confirmed that the CCT3 mutation interferes with CCT's ability to bind a Q/N-rich protein aggregate. This demonstrates that CCT3 has unique substrate specificity for Q/N-rich proteins among the eight CCT subunits. High-throughput microscopy, in vitro gel-shift assay, ATP-binding site mutagenesis, structural modeling Proceedings of the National Academy of Sciences of the United States of America High 23112166
2015 CCT3 depletion in hepatocellular carcinoma (HCC) cells suppresses cell proliferation by inducing mitotic arrest at prometaphase and eventual apoptosis. CCT3 was identified as a novel regulator of spindle integrity and a requirement for proper kinetochore-microtubule attachment during mitosis. CCT3 depletion also sensitizes HCC cells to the microtubule-destabilizing drug vincristine. siRNA knockdown, cell proliferation assay, immunofluorescence microscopy of mitotic spindles and kinetochores, drug sensitivity assay Cancer letters Medium 26739059
2019 Mass spectrometry revealed that CCT3 co-interacts with YAP and TFCP2 in liver cancer cells. CCT3 prolongs the half-life of YAP and TFCP2 by blocking their ubiquitination caused by PCBP2 in a βTrCP-independent manner. CCT3 was found capable of separating PCBP2-YAP interactions, thereby preventing PCBP2-induced ubiquitination of YAP and TFCP2. PCBP2 directly interacts with YAP via a WB motif-WW domain interaction, and indirectly with TFCP2 via YAP. CCT3 acts as a non-nuclear protein upstream of YAP and TFCP2 to control tumourigenesis. Mass spectrometry, co-immunoprecipitation, ubiquitination assay, protein half-life assay, loss-of-function studies Cell death & disease Medium 31501420
2022 CCT3 functions as a non-canonical RNA-binding protein (RBP) that regulates LINC00326 lncRNA in a chaperonin-independent manner. Perturbation of the CCT3-LINC00326 regulatory network led to decreased lipid accumulation, increased lipid degradation in cellulo, and diminished tumour growth in vivo in hepatocellular carcinoma models. RBP knockdown, transcriptome sequencing, CRISPRa overexpression, in vivo tumor models, sequencing-based RBP-lncRNA interaction mapping Gut Medium 35022268
2018 In Drosophila, CCT3 (a subunit of the TRiC/CCT chaperonin complex) physically and genetically interacts with the FNDC3-ortholog MTGO (Miles to go). Larvae heterozygous for a CCT3 mutation that reduces CCT3-MTGO binding show abnormal neuromuscular junction (NMJ) development similar to mtgo null mutants, with dramatically reduced branching, fewer synaptic boutons, and fewer boutons compared with controls. This establishes a functional interaction between CCT3 and MTGO required for NMJ development. Genetic interaction analysis, loss-of-function mutants, confocal microscopy of NMJ, co-immunoprecipitation Developmental biology Medium 30539716
2021 CCT3 suppression in breast cancer (CRL-2329) and prostate cancer (PC3) cells via miRNA mimics (miR-24-3p, miR-128-3p, miR-149-5p) causes G0/G1 cell cycle arrest, impairment of mitochondrial membrane potential, increased intracellular ROS, and induction of apoptosis. CCT3 suppression also shifts intracellular levels of free amino acids involved in energy metabolism (glutamine, beta-alanine, glycine, serine, asparagine, sarcosine), indicating a role for CCT3 in maintaining cellular energy homeostasis. miRNA mimic transfection, flow cytometry, ROS measurement, mitochondrial membrane potential assay, amino acid profiling, Annexin V/PI staining Free radical biology & medicine Medium 33508424
2022 CCT3 knockdown in lung adenocarcinoma (LUAD) cells significantly inhibits glycolysis and reduces total intracellular ATP levels by at least 25%. CCT3 was found to interact with eukaryotic translation initiation factor 3G (EIF3G) by co-immunoprecipitation, and CCT3 depletion reduces EIF3G protein levels and impairs cytoplasmic protein translation. EIF3G-deficient cells show consistent impaired protein synthesis and cell growth, parallel to CCT3 knockdown phenotypes. siRNA knockdown, glycolysis assay, ATP measurement, co-immunoprecipitation, western blot, in vivo xenograft International journal of molecular sciences Medium 35409343
2024 CCT3 interacts with ACTN4 (confirmed by co-immunoprecipitation), and this interaction hinders the recycling of transferrin receptor protein 1 (TFRC) to the cell membrane, thereby obstructing iron endocytosis and inhibiting ferroptosis. The ferroptosis-inhibitory function of CCT3 depends on deubiquitination of K6-linked non-degradative ubiquitination at its lysine 21 (K21), which occurs upon sorafenib treatment. CCT3 knockdown sensitizes HCC cells to sorafenib-induced ferroptosis both in vitro and in vivo. CRISPR/Cas9 screen, PTM omics, co-immunoprecipitation, ferroptosis assays, in vivo xenograft, ubiquitination assays Journal of experimental & clinical cancer research : CR Medium 39210442
2021 CCT3 knockdown in breast cancer cells (HCC1937 and MDA-MB-231) reduces proliferation and migration, increases the proportion of cells in S phase, and induces apoptosis. A rescue experiment showed that overexpression of NFκB-p65 rescues the cell proliferation and migration defects caused by CCT3 knockdown, placing CCT3 upstream of the NFκB-p65 signaling axis in breast cancer cells. Lentiviral shRNA knockdown, Celigo image cytometry, MTT assay, Transwell migration assay, flow cytometry, western blot, rescue experiment Cancer cell international Medium 32518527
2021 CCT3 knockdown in melanoma cells inhibits cell proliferation and cell cycle progression and induces apoptosis. Gene array analysis after CCT3 knockdown showed decreased expression of cyclins and cell cycle regulatory genes. CDK1 expression was significantly decreased after CCT3 knockdown, and functional rescue experiments demonstrated that CDK1 overexpression rescues the decreased cell proliferation caused by CCT3 silencing, placing CCT3 upstream of CDK1 in melanoma. shRNA knockdown, gene array analysis, western blot, functional rescue with CDK1 overexpression, in vivo xenograft Journal of Cancer Medium 35399722
2021 CCT3 promotes cisplatin resistance in lung adenocarcinoma A549/DDP cells via activation of the JAK2/STAT3 pathway. CCT3 knockdown by shRNA re-sensitizes cisplatin-resistant cells to cisplatin, inhibits JAK2/STAT3 signaling, and reduces proliferation, invasion, and migration while inducing G2/M arrest and apoptosis both in vitro and in vivo. shRNA knockdown, western blot of JAK2/STAT3 pathway, cell viability assay, apoptosis assay, in vivo xenograft Bioengineered Low 34612768
2024 CCT3 knockdown in bladder cancer cells induces ferroptosis and suppresses the NOD1-NF-κB signaling pathway. CCT3 silencing suppressed NOD1 and phospho-IκBα expression, and a NOD1 agonist reversed the effects of CCT3 suppression, functionally linking CCT3 to the NOD1-NF-κB axis in bladder cancer. siRNA knockdown, RNA sequencing, western blot, NOD1 agonist rescue, in vivo xenograft, ferroptosis marker analysis Scientific reports Low 39478031
2024 CCT3 was identified as a driver of clear cell renal carcinoma (ccRCC) progression by enhancing XPO1 stability via correct folding, confirmed by Co-IP and GST pull-down assays. This promotes nuclear export of tumor suppressors RB1 and p21, suppressing cellular senescence. CCT3 depletion induced G1 phase arrest and promoted cellular senescence. Combined CCT3 knockdown with XPO1 inhibitor selinexor significantly suppressed tumor growth in xenograft models. Co-IP, GST pull-down, senescence assays (SA-β-gal), cell cycle analysis, in vivo xenograft, western blot iScience Medium 41732260
2025 The apical domains of CCT3 and CCT7 from humans are strong inhibitors of tau aggregation. Kinetic analyses and negative-stain electron microscopy show that the mechanism of inhibition differs between the two subunits: tau aggregation alone or with CCT7 apical domain fits a fragmentation model, whereas with CCT3 apical domain it fits a saturating elongation and fragmentation mechanism. Coarse-grained molecular dynamics simulations reveal that tau interacts with different regions of the CCT3 and CCT7 apical domains. In vitro aggregation kinetics, negative-stain electron microscopy, coarse-grained molecular dynamics simulation Protein science : a publication of the Protein Society Medium 40400346
2026 In zebrafish cct3 loss-of-function mutants, Cct3 is required for normal myelin sheath formation, survival of neural crest-derived Schwann cells, neuromuscular junction (NMJ) developmental refinement, and axonal transport of organelles in peripheral motor axons. Cytoskeletal alterations including disrupted tubulin/microtubule organization were observed. Electron microscopy comparison with human patient-derived tissue confirmed conservation of these pathological features. Cct3 loss caused early apoptotic death of Schwann cells and failed NMJ refinement, paralleling observations in TRiCopathy patients. CRISPR/Cas9 loss-of-function, confocal microscopy with transgenic reporter lines, electron microscopy, immunostaining, comparison with human patient tissue Cell death & disease High 41680121
2016 CCT3 suppression in breast cancer cells inhibits proliferation. CCT3 mRNA levels may be regulated via a ceRNA network involving miR-223 and β-catenin, with CCT3 and β-catenin identified as direct targets of miR-223. CCT3 overexpression was found to activate the Wnt/β-catenin signaling pathway. (NOTE: the original paper PMID:33072568 was subsequently retracted per PMIDs 40078191 and 40104503; findings should be treated with caution.) Luciferase reporter assay, western blot, in vitro/in vivo tumor models, miRNA target validation Frontiers in oncology Low 33072568
2021 CCT3 knockdown in cervical squamous cell carcinoma cells suppresses proliferation, migration, and invasiveness and promotes apoptosis and cell cycle arrest. Rescue experiments demonstrated that CCT3 promotes cervical cancer cell proliferation and migration via fibronectin 1 (FN1): CCT3 knockdown suppressed FN1 protein expression, and FN1 overexpression rescued the proliferation and migration defects caused by CCT3 knockdown. siRNA knockdown, Transwell assay, flow cytometry, western blot, rescue experiment with FN1 overexpression Molecular medicine reports Low 34651664
2016 The CCT complex (of which CCT3 is a subunit) inhibits stress granule assembly in human cells, as demonstrated by proteomic analysis of purified stress granule cores. Multiple ATP-driven machines differentially affect stress granules, with the CCT complex acting as an inhibitor of assembly. Super-resolution microscopy, stress granule core purification, quantitative proteomics Cell Medium 26777405

Source papers

Stage 0 corpus · 129 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2001 Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science (New York, N.Y.) 936 11486088
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2016 An improved smaller biotin ligase for BioID proximity labeling. Molecular biology of the cell 665 26912792
2015 Gene essentiality and synthetic lethality in haploid human cells. Science (New York, N.Y.) 657 26472760
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2006 Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 517 17110338
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2013 The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. The Journal of biological chemistry 413 23463506
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2010 Genome-wide association study of hematological and biochemical traits in a Japanese population. Nature genetics 406 20139978
2005 Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proceedings of the National Academy of Sciences of the United States of America 383 16009940
2015 Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nature methods 370 26414014
2022 The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma. Nature communications 112 36028483
2003 Confirmation of the type 2 myotonic dystrophy (CCTG)n expansion mutation in patients with proximal myotonic myopathy/proximal myotonic dystrophy of different European origins: a single shared haplotype indicates an ancestral founder effect. American journal of human genetics 111 12970845
2022 Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies. Nature communications 104 35750695
2015 Molecular chaperone CCT3 supports proper mitotic progression and cell proliferation in hepatocellular carcinoma cells. Cancer letters 68 26739059
2010 Mutant (CCTG)n expansion causes abnormal expression of zinc finger protein 9 (ZNF9) in myotonic dystrophy type 2. The American journal of pathology 61 20971734
2006 Cognitive-behavioral intervention to enhance adherence to antiretroviral therapy: a randomized controlled trial (CCTG 578). AIDS (London, England) 60 16816559
2006 Quantitative actin folding reactions using yeast CCT purified via an internal tag in the CCT3/gamma subunit. Journal of molecular biology 57 16762366
2016 Expression and diagnostic value of CCT3 and IQGAP3 in hepatocellular carcinoma. Cancer cell international 54 27390551
2019 CCT3 acts upstream of YAP and TFCP2 as a potential target and tumour biomarker in liver cancer. Cell death & disease 53 31501420
2019 A Phase Ib Trial of Durvalumab in Combination with Trastuzumab in HER2-Positive Metastatic Breast Cancer (CCTG IND.229). The oncologist 52 31420468
2004 Hairpin structure-forming propensity of the (CCTG.CAGG) tetranucleotide repeats contributes to the genetic instability associated with myotonic dystrophy type 2. The Journal of biological chemistry 50 15292165
2022 CCT3-LINC00326 axis regulates hepatocarcinogenic lipid metabolism. Gut 49 35022268
2004 Biomolecular identification of (CCTG)n mutation in myotonic dystrophy type 2 (DM2) by FISH on muscle biopsy. European journal of histochemistry : EJH 48 15718211
2018 Canadian Cancer Trials Group (CCTG) IND211: A randomized trial of pelareorep (Reolysin) in patients with previously treated advanced or metastatic non-small cell lung cancer receiving standard salvage therapy. Lung cancer (Amsterdam, Netherlands) 45 29748010
2004 Homozygosity for CCTG mutation in myotonic dystrophy type 2. Brain : a journal of neurology 45 15231584
2005 Effect of the [CCTG]n repeat expansion on ZNF9 expression in myotonic dystrophy type II (DM2). Biochimica et biophysica acta 41 16376058
2021 CCTG BR34: A Randomized Phase 2 Trial of Durvalumab and Tremelimumab With or Without Platinum-Based Chemotherapy in Patients With Metastatic NSCLC. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 36 34800700
2010 Longest form of CCTG microsatellite repeat in the promoter of the CD2BP1/PSTPIP1 gene is associated with aseptic abscesses and with Crohn disease in French patients. Digestive diseases and sciences 35 19731031
2004 New methods for molecular diagnosis and demonstration of the (CCTG)n mutation in myotonic dystrophy type 2 (DM2). Neuromuscular disorders : NMD 35 15019706
2012 Interactions of subunit CCT3 in the yeast chaperonin CCT/TRiC with Q/N-rich proteins revealed by high-throughput microscopy analysis. Proceedings of the National Academy of Sciences of the United States of America 32 23112166
2021 CCT3 suppression prompts apoptotic machinery through oxidative stress and energy deprivation in breast and prostate cancers. Free radical biology & medicine 31 33508424
2019 A phase I study of vistusertib (dual mTORC1/2 inhibitor) in patients with previously treated glioblastoma multiforme: a CCTG study. Investigational new drugs 31 31707687
2016 A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 31 27449804
2005 A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575. AIDS (London, England) 30 15718840
2020 Suppression of CCT3 inhibits the proliferation and migration in breast cancer cells. Cancer cell international 29 32518527
2023 Contact Days Associated With Cancer Treatments in the CCTG LY.12 Trial. The oncologist 27 37226534
2019 Selumetinib in patients receiving standard pemetrexed and platinum-based chemotherapy for advanced or metastatic KRAS wildtype or unknown non-squamous non-small cell lung cancer: A randomized, multicenter, phase II study. Canadian Cancer Trials Group (CCTG) IND.219. Lung cancer (Amsterdam, Netherlands) 26 31200828
2018 Suppression of CCT3 inhibits malignant proliferation of human papillary thyroid carcinoma cell. Oncology letters 26 29805652
2009 A Z-DNA sequence reduces slipped-strand structure formation in the myotonic dystrophy type 2 (CCTG) x (CAGG) repeat. Proceedings of the National Academy of Sciences of the United States of America 26 19218442
2023 m6A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression. Epigenetics 25 37092305
2023 Prediction of Adjuvant Gemcitabine Sensitivity in Resectable Pancreatic Adenocarcinoma Using the GemPred RNA Signature: An Ancillary Study of the PRODIGE-24/CCTG PA6 Clinical Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 25 37963313
2020 Upregulation of CCT-3 Induces Breast Cancer Cell Proliferation Through miR-223 Competition and Wnt/β-Catenin Signaling Pathway Activation. Frontiers in oncology 25 33072568
2011 The origin of genetic instability in CCTG repeats. Nucleic acids research 25 21478167
2017 Treatment outcomes for older patients with relapsed/refractory aggressive lymphoma receiving salvage chemotherapy and autologous stem cell transplantation are similar to younger patients: a subgroup analysis from the phase III CCTG LY.12 trial. Annals of oncology : official journal of the European Society for Medical Oncology 24 27993811
2013 Uninterrupted CCTG tracts in the myotonic dystrophy type 2 associated locus. Neuromuscular disorders : NMD 24 23561036
2021 Upregulation of CCT3 promotes cervical cancer progression through FN1. Molecular medicine reports 23 34651664
2024 CCT3/ACTN4/TFRC axis protects hepatocellular carcinoma cells from ferroptosis by inhibiting iron endocytosis. Journal of experimental & clinical cancer research : CR 22 39210442
2018 Effects of Celecoxib and Low-dose Aspirin on Outcomes in Adjuvant Aromatase Inhibitor-Treated Patients: CCTG MA.27. Journal of the National Cancer Institute 22 29554282
2017 Vitamin D Levels, Vitamin D Receptor Polymorphisms, and Inflammatory Cytokines in Aromatase Inhibitor-Induced Arthralgias: An Analysis of CCTG MA.27. Clinical breast cancer 22 29128193
2012 The unstable CCTG repeat responsible for myotonic dystrophy type 2 originates from an AluSx element insertion into an early primate genome. PloS one 20 22723857
2022 Circular RNA circ-CCT3 promotes bortezomib resistance in multiple myeloma via modulating miR-223-3p/BRD4 axis. Anti-cancer drugs 19 34387610
2021 Chaperonin containing TCP1 subunit 3 (CCT3) promotes cisplatin resistance of lung adenocarcinoma cells through targeting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway. Bioengineered 19 34612768
1996 Cloning, structure and mRNA expression of human Cctg, which encodes the chaperonin subunit CCT gamma. The Biochemical journal 19 8573069
2022 Current understanding on the role of CCT3 in cancer research. Frontiers in oncology 18 36185198
2017 Outcomes in women with invasive ductal or invasive lobular early stage breast cancer treated with anastrozole or exemestane in CCTG (NCIC CTG) MA.27. European journal of cancer (Oxford, England : 1990) 17 29274617
2015 New insights into the genetic instability in CCTG repeats. FEBS letters 17 26384951
2006 DM2 CCTG*CAGG repeats are crossover hotspots that are more prone to expansions than the DM1 CTG*CAG repeats in Escherichia coli. Journal of molecular biology 16 16753177
2017 Phase III trial comparing UFT + PSK to UFT + LV in stage IIB, III colorectal cancer (MCSGO-CCTG). Surgery today 15 28634730
2009 Genetic instabilities of (CCTG).(CAGG) and (ATTCT).(AGAAT) disease-associated repeats reveal multiple pathways for repeat deletion. Molecular carcinogenesis 15 19306311
2017 Expanded [CCTG]n repetitions are not associated with abnormal methylation at the CNBP locus in myotonic dystrophy type 2 (DM2) patients. Biochimica et biophysica acta. Molecular basis of disease 13 29291944
2021 Cancer Antigen 15-3/Mucin 1 Levels in CCTG MA.32: A Breast Cancer Randomized Trial of Metformin vs Placebo. JNCI cancer spectrum 12 34485814
2022 Suppression of CCT3 Inhibits Tumor Progression by Impairing ATP Production and Cytoplasmic Translation in Lung Adenocarcinoma. International journal of molecular sciences 11 35409343
2021 Circular RNA circ‑CCT3 promotes hepatocellular carcinoma progression by regulating the miR‑1287‑5p/TEAD1/PTCH1/LOX axis. Molecular medicine reports 11 33760147
2018 Miles to go (mtgo) encodes FNDC3 proteins that interact with the chaperonin subunit CCT3 and are required for NMJ branching and growth in Drosophila. Developmental biology 11 30539716
2016 BRM Promoter Polymorphisms and Survival of Advanced Non-Small Cell Lung Cancer Patients in the Princess Margaret Cohort and CCTG BR.24 Trial. Clinical cancer research : an official journal of the American Association for Cancer Research 11 27827316
2018 Canadian Cancer Trials Group (CCTG) IND215: A phase Ib study of Selumetinib in patients with untreated advanced or metastatic NSCLC who are receiving standard chemotherapy regimens. Investigational new drugs 10 30317534
2016 Unusual structures of CCTG repeats and their participation in repeat expansion. Biomolecular concepts 10 27879482
2016 The competing mini-dumbbell mechanism: new insights into CCTG repeat expansion. Signal transduction and targeted therapy 10 29263904
2014 Eosinophilic myositis as first manifestation in a patient with type 2 myotonic dystrophy CCTG expansion mutation and rheumatoid arthritis. Neuromuscular disorders : NMD 10 25443993
2024 Repurposing cyclovirobuxine D as a novel inhibitor of colorectal cancer progression via modulating the CCT3/YAP axis. British journal of pharmacology 9 38992898
2022 Suppression of CCT3 inhibits melanoma cell proliferation by downregulating CDK1 expression. Journal of Cancer 9 35399722
2008 Colocalization of ribonuclear inclusions with muscle blind like-proteins in a family with myotonic dystrophy type 2 associated with a short CCTG expansion. Journal of the neurological sciences 9 18804219
2023 Circular RNA CCT3 is a unique molecular marker in bladder cancer. BMC cancer 8 37833621
2025 Exosomal CCT3 as a biomarker for diagnosis and immune therapy response in patients diagnosed with hepatocellular carcinoma. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 7 40221386
1994 Assignment of the human homologue of the mTRiC-P5 gene (TRIC5) to band 1q23 by fluorescence in situ hybridization. Genomics 7 8001976
2023 Metformin, placebo, and endocrine therapy discontinuation among participants in a randomized double-blind trial of metformin vs placebo in hormone receptor-positive early-stage breast cancer (CCTG MA32). Breast cancer research and treatment 6 37157006
2022 Insights into the roles and driving forces of CCT3 in human tumors. Frontiers in pharmacology 6 36313331
2024 A Phase II Study of Neoadjuvant Opnurasib KRAS G12C Inhibitor in Patients With Surgically Resectable Non-Small Cell Lung Cancer (CCTG IND.242A): A Substudy of the IND.242 Platform Master Protocol. Clinical lung cancer 5 39394034
2023 Integrated analyzes identify CCT3 as a modulator to shape immunosuppressive tumor microenvironment in lung adenocarcinoma. BMC cancer 4 36918801
2015 Optimization PCR for Detection CTG/CCTG-Repeat Expansions in the Diagnosis of Myotonic Dystrophies. Annals of clinical and laboratory science 4 26586700
2025 Inhibition of tau aggregation by the CCT3 and CCT7 apical domains. Protein science : a publication of the Protein Society 3 40400346
2024 Massive contractions of myotonic dystrophy type 2-associated CCTG tetranucleotide repeats occur via double-strand break repair with distinct requirements for DNA helicases. G3 (Bethesda, Md.) 3 37950892
2024 Dysfunction of CCT3-associated network signals for the critical state during progression of hepatocellular carcinoma. Biochimica et biophysica acta. Molecular basis of disease 3 38360074
2024 Silencing CCT3 induces ferroptosis through the NOD1-NF-κB signaling pathway in bladder cancer. Scientific reports 3 39478031
2022 Corrigendum: Upregulation of CCT-3 Induces Breast Cancer Cell Proliferation Through miR-223 Competition and Wnt/b-Catenin Signaling Pathway Activation. Frontiers in oncology 3 35664779
2021 Evaluating the Indirect Costs of Care Associated with Salvage Chemotherapy for Relapsed and Refractory Aggressive-Histology Lymphoma: A Subset Analysis of the Canadian Cancer Trials Group (CCTG) LY.12 Clinical Trial. Current oncology (Toronto, Ont.) 3 33802634
2020 Variation in the UGT2B17 genotype, exemestane metabolism and menopause-related toxicities in the CCTG MAP.3 trial. Breast cancer research and treatment 3 32715442
1996 Drosophila melanogaster P1 genomic clone DS05563 contains the chaperonin-encoding gene Cctg. Gene 3 8666276
2024 Co-occurrence of CAPN3 homozygous mutation and CCTG expansion in the CNBP gene in a patient with muscular dystrophy. Postepy psychiatrii neurologii 2 39119544
2024 Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial. Journal for immunotherapy of cancer 2 39631846
1996 Molecular characterisation of the Xenopus laevis chaperonin gene Cctg. Biochimica et biophysica acta 2 8950171
2025 Advances in the study of CCT3 in malignant tumors: A review. Medicine 1 39928781
2025 Modulating CCTG repeat expansion toxicity in DM2 Drosophila model through TDP1 inhibition. EMBO molecular medicine 1 40133672
2018 Myotonic Dystrophy-2: Unusual Phenotype Due to a Small CCTG-expansion. Balkan journal of medical genetics : BJMG 1 30984523
2026 CCT3 Facilitates the Malignant Progression of NSCLC and SCLC via PI3 K/AKT-EMT Axis and Emerges as a Novel Serum Diagnostic Biomarker. Technology in cancer research & treatment 0 41505338
2026 The chaperonin TRiC component Cct3 is required for axonal transport, myelination, and neuromuscular junction refinement. Cell death & disease 0 41680121
2026 CCT3-mediated regulation of XPO1/RB1 axis stability promotes cellular senescence and tumor progression in clear cell renal carcinoma. iScience 0 41732260
2025 Retraction: Upregulation of CCT-3 induces breast cancer cell proliferation through miR-223 competition and Wnt/β-catenin signaling pathway activation. Frontiers in oncology 0 40078191
2025 Retraction: Corrigendum: Upregulation of CCT-3 induces breast cancer cell proliferation through miR-223 competition and Wnt/b-catenin signaling pathway activation. Frontiers in oncology 0 40104503
2025 Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data. Immunotherapy 0 40184324
2025 Continuous versus Standard Palbociclib Treatment and Molecular Profiling of Solid Tissues and Liquid Biopsies in the CCTG MA.38 Trial in Advanced Breast Cancer. Cancer research communications 0 41123599
2025 A Retrospective Study in Colorectal Adenocarcinoma Uncovers the Potential of Circ-CCT3 as a Predictor of Tumor Recurrence. Biomedicines 0 41153715
2025 Effects of serotonergic drugs on immune checkpoint inhibitor response: a pooled analysis of individual patient data from four Canadian Cancer Trials Group (CCTG) trials. Immunotherapy 0 41175109
2025 Dihydroartemisinin: A Targeting Agent of CCT3-Mediated Oxidative Stress to Enhance the Antitumor Activity of Doxorubicin in Hepatocellular Carcinoma. Digestive diseases and sciences 0 41205108
2024 Effects of interrupting residues on DNA dumbbell structures formed by CCTG tetranucleotide repeats associated with myotonic dystrophy type 2. FEBS letters 0 38922834
2023 Massive contractions of Myotonic Dystrophy Type 2-associated CCTG tetranucleotide repeats occur via double strand break repair with distinct requirements for helicases. bioRxiv : the preprint server for biology 0 37461657
2021 Predicting the clinical outcomes and benefit from letrozole after 5 years of treatment with aromatase inhibitors for early breast cancer: analysis from CCTG MA.17R. Breast cancer research and treatment 0 34825307
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